MMPs as prognostic markers
Surgical removal of the tumor is the standard treatment pro-
cedure for most cancer types. Usually, surgery is followed by
adjuvant therapy like radiation, chemotherapy, hormones, an-
giogenic inhibitors, or kinase inhibitors. All these treatment
procedures may cause harmful side effects, and some patients
may be over-treated because of failure to identify those with
low risk of cancer recurrence. Other patients could benefit
from more aggressive treatment. During the last decade, new
biomarkers which can predict the chance of relapse have been
identified and are helpful in treatment stratification.
An overwhelming number of studies have addressed the
potential of MMPs and their tissue inhibitors, TIMPS, as
prognostic markers in different cancer types. Despite the huge
number of studies, it is difficult to draw general conclusions
regarding the prognostic value of specific MMPs or TIMPS in
different types of cancer because the results are often
conflicting. There are many possible reasons for this. First,
as stated in the introduction, the MMPs are multifunctional
enzymes and the role of a specific enzyme is dependent on
which substrates it acts on in a given biological setting. This is
likely to vary between patients, between organs, and between
different phases of cancer development and progression. TIMPs are also multifaceted proteins, and their MMP-
independent functions are only starting to be revealed.
Furthermore, differences in study design make it difficult to
compare studies. In some studies, the level of MMPs or
TIMPs in blood or urine is measured, whereas other look at
MMP or TIMP expression in tissue samples or tissue extracts.
Some measure enzyme activity, whereas others quantify total
expression at transcriptional or protein level. Also, when
examining protein expression, some studies separate active
enzymes and pro-enzymes, some specify the MMP- or TIMP-
expressing cell types, whereas others look at total expression.
Furthermore, there are a huge number of different antibodies
used and no general agreements upon a set of well-tested and
validated antibodies and protocols. Together, these factors are
likely to explain some of the contradicting reports regarding
prognostic value of MMPs in cancer patients. In the following
part, we will give some examples of studies exploring the
prognostic value of MMPs and TIMPs in four of the most
common cancer types. Due to the large number of studies, this
is not a review of the total number of relevant publications but
a selection, highlighting trends and contradictions.